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(1) Background: This study investigated the impact of in vitro adaptations to acid and bile stress on the cholesterol-lowering activity of the probiotic Lactobacillus kefir M20. (2) Methods: Lactobacillus kefir M20 was extracted from fermented dairy products in Xinjiang, China, and isolated using MRS medium. The lactic acid bacteria were cultured for stress resistance to acid and bile salts and then gavaged into mice for animal experiments. (3) Results: The adaptation to bile stress treatment resulted in a notable enhancement of the cholesterol-lowering capacity of Lactobacillus kefir M20, with reductions of 16.5% and 33.1% in total and non-HDL cholesterol, respectively, compared to the untreated strain. Furthermore, the daily fecal total bile acid excretion was 9.2, 5.4 and 5.0 times higher in the M20-BSA group compared to the HC, M20 and M20-ASA groups, respectively. (4) Conclusions: This study suggests that targeted probiotics have the potential for application in the next generation of functional foods and probiotic formulations aimed at combating hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Background: Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Based on previous studies in tumor-bearing mice, this study evaluated the biodistribution of the sodium salt of cobaltabis(dicarbollide) (Na[3,3′-Co(C2B9H11)2], abbreviated as Na[o-COSAN]) in the hamster cheek pouch oral cancer model and the Na[o-COSAN]/BNCT therapeutic effect on tumors and induced radiotoxicity. The synthesis and comprehensive characterization of 10B-enriched trimethylammonium salt of nido-[7,8-C210B9H12]−o-carborane, along with the cesium and sodium salts of [o-10COSAN] cobaltabis(dicarbollide) are reported here for the first time. Methods: Hamsters bearing tumors were injected with Na[o-COSAN] (7.5 mg B/kg) and euthanized at different time-points after injection (30 min, 2, 3, 5, and 18 h post-administration) to evaluate boron uptake in different tissues/organs. Based on these results, tumor-bearing animals were treated with Na[10B-o-COSAN]/BNCT (7.5 mg B/kg b.w., 3 h), prescribing 5 Gy total in absorbed dose to the precancerous tissue surrounding tumors, i.e., the dose-limiting tissue. Results: Na[o-10COSAN] exhibited no toxicity. Although biodistribution studies employing Na[o-COSAN] have shown low absolute boron concentration in the tumor (approx. 11 ppm), Na[o-10COSAN]/BNCT induced a high and significant therapeutic effect on tumors versus the control group (cancerized, untreated animals). Moreover, only half of the animals exhibited severe mucositis in the precancerous dose-limiting tissue after BNCT, which resolved completely at 21 days after irradiation. Conclusions: Na[o-10COSAN] would be potentially useful to treat head and neck cancer with BNCT. [ABSTRACT FROM AUTHOR]

Background: The use of Caspase-3 to evaluate the chemopreventive effect of quercetin on experimentally induced squamous cell carcinoma was applied in the current study. Materials and Methods: Five groups of Syrian male hamsters were employed in the study. Group I (negative control): 5 animals do not receive any treatment. Group II: 5 animals receiving (quercetin only at a concentration of 150 mg/kg). Group III (dimethylbenz(a)anthracene [DMBA]-treated group for 14 weeks): 10 animals were coated with 0.5% DMBA. Group IV (DMBA + quercetin 150 mg/kg): 15 animals receiving quercetin of a concentration (150 mg/kg) every day through a gavage tube along with painting the hamster buccal pouch with DMBA (0.5%) three times per week for 14 weeks. Group V (DMBA + quercetin 50 mg/kg): 15 animals receiving quercetin of concentration (50 mg/kg) every day through a gavage tube along with painting the hamster buccal pouch with DMBA (0.5%) for 14 weeks at three times each week. Results: Group III showed the lowest mean area percent (10.23), whereas Group V revealed the highest mean area percent value (23.64). All groups showed a statistically significant difference among them. Conclusion: Quercetin showed apoptotic potential validated by Caspase-3, so it may be a valuable chemopreventive agent antagonizing DMBA-induced carcinogenesis in animal models.

Rodents are commonly used as animal models in studies investigating various experimental conditions, often requiring gene expression analysis. Quantitative real-time reverse transcription PCR (RT-qPCR) is the most widely used tool to quantify target gene expression levels under different experimental conditions in various biological samples. Relative normalization with reference genes is a crucial step in RT-qPCR to obtain reliable quantification results. In this work, the main reference genes used in gene expression studies among the three rodents commonly employed in scientific research—hamster, rat, and mouse—are analyzed and described. An individual literature search for each rodent was conducted using specific search terms in three databases: PubMed, Scopus, and Web of Science. A total of 157 articles were selected (rats = 73, mice = 79, and hamsters = 5), identifying various reference genes. The most commonly used reference genes were analyzed according to each rodent, sample type, and experimental condition evaluated, revealing a great variability in the stability of each gene across different samples and conditions. Classic genes, which are expected to be stably expressed in both samples and conditions analyzed, demonstrated greater variability, corroborating existing concerns about the use of these genes. Therefore, this review provides important insights for researchers seeking to identify suitable reference genes for their validation studies in rodents. [ABSTRACT FROM AUTHOR]

The mortality and hospitalization rate by COVID‐19 dropped significantly currently, but its seasonal outbreaks make antiviral treatment still vital. The mortality and hospitazation rate by COVID‐19 dropped significantly currently, but its seasonal ourbreaks make antiviral treatment still vital. In our study, syrian golden hamsters were treated with molnupiravir and interferons (IFNs) after SARS‐CoV‐2 infection. Their weight changes, pathological changes, virus replication and inflammation levels were evaluated. In the IFNs single treatment, only IFN‐α group reduced viral load (p < 0.05) and virus titer in hamster lungs. The TNF‐α expression decreased significantly in both IFNs treatment at 2dpi. Histological and immunofluorescence results showed lung damage in the IFNs groups were milder at 4dpi. In the molnupiravir/IFN‐α combination treatment, weight loss and virus replication in lung were significantly decreased in the mono‐molnupiravir group and combination group (p < 0.05), the expression of IL‐6, TNF‐α, IL‐1β and MIP‐1α also decreased significantly (p < 0.05), but the combination treatment was not more effective than the mono‐molnupiravir treatment. Histological and immunofluorescence results showed the lung damage and inflammation in mono‐molnupiravir and combination groups were milder. In summary, IFNs treatment had anti‐inflammatory effect against SARS‐CoV‐2, only IFN‐α showed a weak antiviral effect. Molnupiravir/IFN‐α combination treatment was effective against SARS‐CoV‐2 but was not superior to mono‐molnupiravir treatment. IFN‐α could be considered for immunocompromised patients to stimulate and activate early immune responses. [ABSTRACT FROM AUTHOR]

Adenovirus infections of immunocompromised patients can cause life-threatening disseminated disease. While there are presently no drugs specifically approved to treat these infections, there are several compounds that showed efficacy against adenovirus in preclinical studies. For any such compound, low toxicity is an essential requirement. As cumulative drug effects can accentuate pathology, especially in patients with other morbidities, it is important to limit antiviral exposure to what is absolutely necessary. This is achievable by monitoring the virus burden of the patients and administering antivirals to suppress virus replication to a non-pathogenic level. We modeled such a system using Syrian hamsters infected with a replication-competent adenovirus vector, in which luciferase expression is coupled to virus replication. We found that virus replication could be followed in vivo in the same animal by repeated measurement of luciferase expression. To test the utility of an interrupted treatment regimen, we used NPP-669 and valganciclovir, two antiviral compounds with high and moderate anti-adenoviral efficacy, respectively. We found that short-term treatment of adenovirus-infected hamsters at times of peak virus replication can prevent virus-associated pathology. Thus, we believe that this animal model can be used to model different treatment regimens for anti-adenoviral compounds. [ABSTRACT FROM AUTHOR]

ABSTRACT Hantaviruses are rodent-borne viruses that cause severe disease in infected humans. In the New World, major hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV) causing hantavirus pulmonary syndrome. In the Old World, major hantaviruses include Hantaan virus (HTNV) and Puumala virus (PUUV) causing hemorrhagic fever with renal syndrome. Here, we produced a pan-hantavirus therapeutic (SAB-163) comprised of fully human immunoglobulin purified from the plasma of transchromosomic bovines (TcB) vaccinated with hantavirus DNA plasmids coding for the major glycoproteins of ANDV, SNV, HTNV, and PUUV. SAB-163 has potent neutralizing antibodies (PRNT50 > 200,000) against the four targeted hantavirus and cross-neutralization against several other heterotypic hantaviruses. At a dosage of 10 mg/kg, SAB-163 is bioavailable in Syrian hamsters out to 70 days post-treatment with a half-life of 10–15 days. At this same dosage, SAB-163 administered 1 day before, or 5 days after exposure, protected all hamsters from lethal disease caused by ANDV. At a higher dose, partial but significant protection was achieved as late as day 6. SAB-163 also protected hamsters in the HTNV, PUUV, and SNV infection models when administered 1 day before or up to 3 days after challenge. This pan-hantavirus therapeutic is attractive because it is fully human, multi-targeted, safe, stable at 4°C, and effective in animal models. SAB-163 was evaluated for safety in GLP human tissue binding studies and a GLP rabbit toxicity study at 365 and 730 mg/kg and is investigational new drug enabled for phase 1 clinical trial(s).IMPORTANCEThis candidate polyclonal human IgG product was produced using synthetic gene-based vaccines and transgenic cows. Having now gone through cGMP production, GLP safety testing, and efficacy testing in animals, SAB-163 is the world’s most advanced anti-hantavirus antibody-based medical countermeasure, aside from convalescent human plasma. Importantly, SAB-163 targets the most prevalent hantaviruses on four continents.

Summary: Background: Post-acute sequalae of COVID-19 defines a wide range of ongoing symptoms and conditions long after SARS-CoV-2 infection including respiratory diseases. The histopathological changes in the lung and underlying mechanism remain elusive. Methods: We investigated lung histopathological and transcriptional changes in SARS-CoV-2-infected male hamsters at 7, 14, 42, 84 and 120dpi, and compared with A (H1N1)pdm09 infection. Findings: We demonstrated viral residue, inflammatory and fibrotic changes in lung after SARS-CoV-2 but not H1N1 infection. The most prominent histopathological lesion was multifocal alveolar-bronchiolization observed in every SARS-CoV-2 infected hamster (31/31), from 42dpi to 120dpi. Proliferating (Ki67+) CK14+ basal cells accumulated in alveoli adjacent to bronchioles at 7dpi, where they proliferated and differentiated into SCGB1A+ club cell or Tubulin+ ciliated cells forming alveolar-bronchiolization foci. Molecularly, Notch pathway significantly upregulated with intensive Notch3 and Hes1 protein expression in alveolar-bronchiolization foci at 42 and 120dpi, suggesting Notch signaling involving the persistence of alveolar-bronchiolization. This is further demonstrated by spatial transcriptomic analysis. Intriguingly, significant upregulation of some cell-growth promoting pathways and genes such as Tubb4b, Stxbp4, Grb14 and Mlf1 were spatially overlapping with bronchiolization lesion. Interpretation: Incomplete resolution of SARS-CoV-2 infection in lung with viral residue, chronic inflammatory and fibrotic damage and alveolar-bronchiolization impaired respiratory function. Aberrant activation of CK14+ basal cells during tissue regeneration led to persistent alveolar-bronchiolization due to sustained Notch signaling. This study advances our understanding of respiratory PASC, sheds light on disease management and highlights the necessity for monitoring disease progression in people with respiratory PASC. Funding: Funding is listed in the Acknowledgements section.

Epitheliotropic cutaneous T‐cell lymphoma (ETCL) is rarely described in golden or Syrian hamsters (Mesocricetus auratus), and no effective treatments or outcomes have previously been published. This study includes two cases of epitheliotropic cutaneous T‐cell lymphoma that were diagnosed via skin biopsy. Clinical presentation, diagnosis, treatment and outcome were reported. Both cases received chemotherapy, including prednisolone, lomustine, L‐asparaginase and chlorambucil. One Syrian hamster that received prednisolone (0.5 mg/kg per os every 24 hours) and chlorambucil (0.4 mg/kg per os every 24 hours) survived 276 days after diagnosis. Another Syrian hamster treated with prednisolone (1 mg/kg per os every 24 hours) survived 81 days after diagnosis. The effectiveness of lomustine and L‐asparaginase remains unknown for Syrian hamsters, and more studies are needed to determine appropriate dose ranges for chlorambucil. The combination of chlorambucil (0.4 mg/kg per os every 24 hours) and prednisolone (0.5–1 mg/kg per os every 24 hours) may assist in managing epitheliotropic cutaneous T‐cell lymphoma in Syrian hamsters. [ABSTRACT FROM AUTHOR]

• Waning immunity and new variants necessitate next generation SARS-CoV-2 vaccines. • The M2SR platform has a clear safety and immunogenic profile in clinical testing. • Intranasal dual influenza/COVID-19 vaccine induces systemic and mucosal antibodies. • SARS-CoV-2 M2SR protects hamsters from SARS-CoV-2 infection and lung pathology. • Dual vaccine maintains immunogenicity to matched and drifted influenza strains. The COVID-19 pandemic has highlighted the need for mucosal vaccines as breakthrough infections, short-lived immune responses and emergence of new variants have challenged the efficacy provided by the first generation of vaccines against SARS-CoV-2 viruses. M2SR SARS-CoV-2, an M2-deleted single-replication influenza virus vector modified to encode the SARS-CoV-2 receptor binding domain, was evaluated following intranasal delivery in a hamster challenge model for protection against Wuhan SARS-CoV-2. An adjuvanted inactivated SARS-CoV-2 whole virus vaccine administered intramuscularly was also evaluated. The intranasal M2SR SARS-CoV-2 was more effective than the intramuscular adjuvanted inactivated whole virus vaccine in providing protection against SARS-CoV-2 challenge. M2SR SARS-CoV-2 elicited neutralizing serum antibodies against Wuhan and Omicron SARS-CoV-2 viruses in addition to cross-reactive mucosal antibodies. Furthermore, M2SR SARS-CoV-2 generated serum HAI and mucosal antibody responses against influenza similar to an H3N2 M2SR influenza vaccine. The intranasal dual influenza/COVID M2SR SARS-CoV-2 vaccine has the potential to provide protection against both influenza and COVID. [ABSTRACT FROM AUTHOR]

Onchocerciasis is a devastating skin and eye disease that afflicts about 21 million people, most of whom live in sub-Saharan Africa. Its control with the microfilaricidal drug ivermectin is limited, thus necessitating the development of preclinical animal models to aid in the discovery of a macrofilaricide. Previously, we found that Onchocerca ochengi (the closest relative of the human O. volvulus) worm masses survive better in hamsters than in gerbils. The aim of this study was to compare the survival of O. ochengi adult male worms and their susceptibility to flubendazole (FBZ, a macrofilaricide) in gerbils and hamsters. The animals were intraperitoneally implanted with O. ochengi male worms, treated with FBZ, and sacrificed 35 days post-implantation. Unlike gerbils which had some worms moving freely in the peritoneum and some in newly formed nodules (neo-nodules), all the worms in the hamsters were found in neo-nodules. FBZ significantly decreased worm burden, motility, and viability in gerbils whereas it had no significant effect in hamsters. These results highlight a major difference in how O. ochengi adult male worms are sustained and affected by FBZ in gerbils compared to hamsters. Understanding the difference between these two models is important in the development of effective macrofilaricides for onchocerciasis. [ABSTRACT FROM AUTHOR]

Animal studies are a prerequisite for human clinical studies involving exposures to a new therapeutic approach to test the quality of observations and treatment outcomes. Owing to the possibility of studying periodontal diseases longitudinally on both cellular and molecular levels, animal models, despite their known shortcomings, are considered superior to other study models when providing information at the host level. [ABSTRACT FROM AUTHOR]

The nidicolous tick Ixodes laguri is a nest-dwelling parasite of small mammals that mainly infest rodents of the families Cricetidae, Gliridae, Muridae and Sciuridae. There is no proven vectorial role for I. laguri, although it is suggested that it is a vector of Francisella tularensis. In this study, a first map depicting the entire geographical distribution of I. laguri based on georeferenced locations is presented. For this purpose, a digital data set of 142 georeferenced locations from 16 countries was compiled. Particular attention is paid to the description of the westernmost record of I. laguri in the city of Vienna, Austria. There, I. laguri is specifically associated with its main hosts, the critically endangered European hamster (Cricetus cricetus) and the European ground squirrel (Spermophilus citellus). These two host species have also been mapped in the present paper to estimate the potential distribution of I. laguri in the Vienna metropolitan region. The range of I. laguri extends between 16–108∘ E and 38–54∘ N, i.e. from Vienna in the east of Austria to Ulaanbaatar, the capital of Mongolia. In contrast to tick species that are expanding their range and are also becoming more abundant as a result of global warming, I. laguri has become increasingly rare throughout its range. However, I. laguri is not threatened by climate change, but by anthropogenic influences on its hosts and their habitats, which are typically open grasslands and steppes. Rural habitats are threatened by the intensification of agriculture and semi-urban habitats are increasingly being destroyed by urban development.

The ubiquity of circadian rhythms in living organisms has generally been accepted by researchers over the last century. Indeed, morphology and molecular biology of the circadian clock were described during the last fifty years. This main biological clock is located in the suprachiasmatic nucleus of the hypothalamus. This nucleus is connected with the retina by the retinohypothalamic tract. This way, light regulates the functioning of the biological clock and biological rhythms such as the sleep-wake cycle and other cyclic functions by releasing melatonin from the pineal body (PB) into the general circulation. Melatonin reaches the retina via the bloodstream as humoral feedback. More than a hundred years ago a reverse neuronal connection between the central nervous system and the retina was hypothesized. This so-called centrifugal visual or retinopetal system has been explored in detail in birds, but less information is available in mammals. In this work, the morphology and physiology of mammalian centrifugal visual pathways are reviewed. It is generally accepted that the centrifugal (retinopetal) fibers terminate mainly on the amacrine cells of the retina. Histaminergic fibers terminate on dopaminergic amacrine cells. Serotoninergic synapses were identified on ganglion cells. In addition, serotoninergic fibers were also associated with photoreceptor terminals. Luteinizing hormone releasing hormone fibers have been observed in birds, but not in mammalian retinas. In summary, based on the data available in the literature, it seems that the retinopetal system has a mandatory role in lower vertebrates, but a modulatory role in mammals. There is currently no adequate way to eliminate the centrifugal visual system that would better explain its true function.

(1) Background: This study investigated the impact of in vitro adaptations to acid and bile stress on the cholesterol-lowering activity of the probiotic Lactobacillus kefir M20. (2) Methods: Lactobacillus kefir M20 was extracted from fermented dairy products in Xinjiang, China, and isolated using MRS medium. The lactic acid bacteria were cultured for stress resistance to acid and bile salts and then gavaged into mice for animal experiments. (3) Results: The adaptation to bile stress treatment resulted in a notable enhancement of the cholesterol-lowering capacity of Lactobacillus kefir M20, with reductions of 16.5% and 33.1% in total and non-HDL cholesterol, respectively, compared to the untreated strain. Furthermore, the daily fecal total bile acid excretion was 9.2, 5.4 and 5.0 times higher in the M20-BSA group compared to the HC, M20 and M20-ASA groups, respectively. (4) Conclusions: This study suggests that targeted probiotics have the potential for application in the next generation of functional foods and probiotic formulations aimed at combating hypercholesterolemia.

The pathologic consequences of Coronavirus Disease-2019 (COVID-19) include elevated inflammation and dysregulated vascular functions associated with thrombosis. In general, disruption of vascular homeostasis and ensuing prothrombotic events are driven by activated platelets, monocytes, and macrophages, which form aggregates (thrombi) attached to the endothelium lining of vessel walls. However, molecular pathways underpinning the pathological interactions between myeloid cells and endothelium during COVID-19 remain undefined. Here, we tested the hypothesis that modulations in the expression of cellular receptors angiotensin-converting enzyme 2 (ACE2), CD147, and glucose-regulated protein 78 (GRP78), which are involved in homeostasis and endothelial performance, are the hallmark responses induced by SARS-CoV-2 infection. Cultured macrophages and lungs of hamster model systems were used to test this hypothesis. The results indicate that while macrophages and endothelial cells are less likely to support SARS-CoV-2 proliferation, these cells may readily respond to inflammatory stimuli generated by the infected lung epithelium. SARS-CoV-2 induced modulations of tested cellular receptors correlated with corresponding changes in the mRNA expression of coagulation cascade regulators and endothelial integrity components in infected hamster lungs. Among these markers, tissue factor (TF) had the best correlation for prothrombotic events during SARS-CoV-2 infection. Furthermore, the single-molecule fluorescence in situ hybridization (smFISH) method alone was sufficient to determine the peak and resolution phases of SARS-CoV-2 infection and enabled screening for cellular markers co-expressed with the virus. These findings suggest possible molecular pathways for exploration of novel drugs capable of blocking the prothrombotic shift events that exacerbate COVID-19 pathophysiology and control the disease. [ABSTRACT FROM AUTHOR]

Pet golden hamsters were first identified being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant of concern (VOC) and transmitted the virus back to humans in Hong Kong in January 2022. Here, we studied the binding of two hamster (golden hamster and Chinese hamster) angiotensinconverting enzyme 2 (ACE2) proteins to the spike protein receptor-binding domains (RBDs) of SARS-CoV-2 prototype and eight variants, including alpha, beta, gamma, delta, and four omicron sub-variants (BA.1, BA.2, BA.3, and BA.4/BA.5). We found that the two hamster ACE2s present slightly lower affinity for the RBDs of all nine SARS-CoV-2 viruses tested than human ACE2 (hACE2). Furthermore, the similar infectivity to host cells expressing hamster ACE2s and hACE2 was confirmed with the nine pseudotyped SARS-CoV-2 viruses. Additionally, we determined two cryo-electron microscopy (EM) complex structures of golden hamster ACE2 (ghACE2)/delta RBD and ghACE2/omicron BA.3 RBD. The residues Q34 and N82, which exist in many rodent ACE2s, are responsible for the lower binding affinity of ghACE2 compared to hACE2. These findings suggest that all SARS-CoV-2 VOCs may infect hamsters, highlighting the necessity of further surveillance of SARS-CoV-2 in these animals. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic required the immediate need to transfer inactivated tissue from biosafety level (BSL)-3 to BSL-1 areas to enable downstream analytical methods. No validated SARS-CoV-2 inactivation protocols were available for either formaldehyde (FA)-fixed or glutaraldehyde (GA)-fixed tissues. Therefore, representative tissue from ferrets and hamsters was spiked with 2.2 × 106 tissue culture infectious dose 50% per ml (TCID50/ml) SARS-CoV-2 or were obtained from mice experimentally infected with SARS-CoV-2. SARS-CoV-2 inactivation was demonstrated with 4% FA or 5% GA at room temperature for 72 hours by a titer reduction of up to 103.8 TCID50/ml in different animal tissues with a maximum protein content of 100 µg/mg and a thickness of up to 10 mm for FA and 8 mm for GA. Our protocols can be easily adapted for validating the inactivation of other pathogens to allow for the transfer of biological samples from BSL-3 areas to BSL-1 laboratories. [ABSTRACT FROM AUTHOR]

Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1pdm09) interactions in Syrian hamsters. H1N1 given 48 h prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by the normalization of granulocyte dynamics and accelerated antigen-presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified a rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 h dual-infected animals. The animals that were infected with both viruses also showed a notable and temporary downregulation of mitochondrial and viral replication pathways. Quantitative RT-PCR confirmed a decrease in the SARS-CoV-2 viral load and lower cytokine levels in the lungs of animals infected with both viruses throughout the course of the disease. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with the mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates. [ABSTRACT FROM AUTHOR]

Opisthorchis viverrini infection is endemic in the lower Mekong subregion. The liver is an organ that worms are drawn to and cause damage. However, the immune-related susceptibility in the liver is poorly understood. In this study, we investigated T helper (Th) cell responses in the liver of BALB/c mice and golden Syrian hamsters during 2–28 days post-infection (DPI). We found that Th cell responses were distinct between mice and hamsters in terms of dynamics and polarization. Mice exhibited the early induction of Th1, Th2, Th17, and regulatory T (Treg) cells responses after the presence of O. viverrini worms at 2 DPI. In hamsters, the late induction of Th1/Th17, downregulation of Th2/Treg responses and early elevation of suppressive cytokine interleukin (IL)-10 were found together with swift reduction of Th cell numbers. Interestingly, expressions of IL-4 (Th2 functional cytokine) and Foxp3 (Treg lineage) were completely different between mice and hamsters which elevated in mice but suppressed in hamsters. These results suggest that early induction and well-regulation are related to host resistance. In contrast, late induction of Th cell response might allow immature worms to develop in the host. Our findings provide a greater understanding in Th cell response-related susceptibility in O. viverrini infection which would be targeting immunity for the development of immune-based intervention such as vaccine. [ABSTRACT FROM AUTHOR]

Leptospirosis is an emerging infectious disease caused by pathogenic Leptospira spp. Humans and some mammals can develop severe forms of leptospirosis accompanied by a dysregulated inflammatory response, which often results in death. The gut microbiota has been increasingly recognized as a vital element in systemic health. However, the precise role of the gut microbiota in severe leptospirosis is still unknown. Here, we aimed to explore the function and potential mechanisms of the gut microbiota in a hamster model of severe leptospirosis. Our study showed that leptospires were able to multiply in the intestine, cause pathological injury, and induce intestinal and systemic inflammatory responses. 16S rRNA gene sequencing analysis revealed that Leptospira infection changed the composition of the gut microbiota of hamsters with an expansion of Proteobacteria. In addition, gut barrier permeability was increased after infection, as reflected by a decrease in the expression of tight junctions. Translocated Proteobacteria were found in the intestinal epithelium of moribund hamsters, as determined by fluorescence in situ hybridization, with elevated lipopolysaccharide (LPS) levels in the serum. Moreover, gut microbiota depletion reduced the survival time, increased the leptospiral load, and promoted the expression of proinflammatory cytokines after Leptospira infection. Intriguingly, fecal filtration and serum from moribund hamsters both increased the transcription of TNF-α, IL-1β, IL-10, and TLR4 in macrophages compared with those from uninfected hamsters. These stimulating activities were inhibited by LPS neutralization using polymyxin B. Based on our findings, we identified an LPS neutralization therapy that significantly improved the survival rates in severe leptospirosis when used in combination with antibiotic therapy or polyclonal antibody therapy. In conclusion, our study not only uncovers the role of the gut microbiota in severe leptospirosis but also provides a therapeutic strategy for severe leptospirosis.

This research aims to create an automatic hamster feeder system at night following the nocturnal nature of hamsters. The system will be given a command in the form of a message via the Telegram messaging application to fill the hamster's weight which will be calculated as a calculation of the hamster's daily feed portion. The nature of hamsters which are generally nocturnal, in contrast to humans who usually rest at night, makes it difficult for humans to feed their hamsters at night regularly. The daily portion of hamster food is around 0.11 times the hamster's body weight and this provision must be appropriate not to cause obesity in the hamster. Based on these circumstances, this research is proposed as a solution to this problem. After filling the hamster's weight information, the system will calculate the hamster's daily food weight and when the sensor catches that the hamster approaching the system, the system will immediately open the servo motor to pour the hamster food.

Abstract Objectives To study clinical disease outcomes in both human and animal models to understand the pathogenicity of omicron compared to the delta variant. Methods In this cross-sectional observational study, clinical outcomes of adults who tested positive at 2 testing centres in Delhi National Capital Region between January 2022 and March 2022 (omicron-infected; N = 2998) were compared to a similar geographical cohort (delta-infected; N = 3292). In addition, disease course and outcomes were studied in SARS-CoV-2-infected golden Syrian hamsters and K-18 humanized ACE2 transgenic mice. Results Omicron variant infection was associated with a milder clinical course [83% (95% CI 61, 94) reduced risk of severity compared against delta] adjusting for vaccination, age, sex, prior infection and occupational risk. This correlated with lower disease index and vir comparing omicron with other variants in animal models. Conclusions Infections caused by the omicron variant were milder compared to those caused by the delta variant independent of previous immunity.

Adenovirus infections of immunocompromised patients can cause life-threatening disseminated disease. While there are presently no drugs specifically approved to treat these infections, there are several compounds that showed efficacy against adenovirus in preclinical studies. For any such compound, low toxicity is an essential requirement. As cumulative drug effects can accentuate pathology, especially in patients with other morbidities, it is important to limit antiviral exposure to what is absolutely necessary. This is achievable by monitoring the virus burden of the patients and administering antivirals to suppress virus replication to a non-pathogenic level. We modeled such a system using Syrian hamsters infected with a replication-competent adenovirus vector, in which luciferase expression is coupled to virus replication. We found that virus replication could be followed in vivo in the same animal by repeated measurement of luciferase expression. To test the utility of an interrupted treatment regimen, we used NPP-669 and valganciclovir, two antiviral compounds with high and moderate anti-adenoviral efficacy, respectively. We found that short-term treatment of adenovirus-infected hamsters at times of peak virus replication can prevent virus-associated pathology. Thus, we believe that this animal model can be used to model different treatment regimens for anti-adenoviral compounds.

Abstract Since SARS-CoV-2 was first reported in late 2019, multiple variations of the original virus have emerged. Each variant harbors accumulations of mutations, particularly within the spike glycoprotein, that are associated with increased viral transmissibility and escape immunity. The different mutations in the spike protein of different variants shape the subsequent antibody and T cell responses, such that exposure to different spike proteins can result in reduced or enhanced responses to heterologous variants further down the line. Globally, people have been exposed and re-exposed to multiple variations of the Ancestral strain, including the five variants of concerns. Studies have shown that the protective immune response of an individual is influenced by which strain or combination of strains they are exposed to. The initial exposure to a specific strain may also shape their subsequent immune patterns and response to later infections with a heterologous virus. Most immunological observations were carried out early during the pandemic when the Ancestral strain was circulating. However, SARS-CoV-2 variants exhibit varying patterns of disease severity, waning immunity, immune evasion and sensitivity to therapeutics. Here we investigated the cross-protection in hamsters previously infected with a variant of concern (VOC) and subsequently re-infected with a heterologous variant. We also determined if cross-protection and immunity were dependent on the specific virus to which the hamster was first exposed. We further profiled the host cytokine response induced by each SARS-CoV-2 variants as well as subsequent to re-infection. A comparative analysis of the three VOCs revealed that Alpha variant was the most pathogenic VOC to emerge. We showed that naturally acquired immunity protected hamsters from subsequent re-infection with heterologous SARS-CoV-2 variant, regardless which variant the animal was first exposed to. Our study supports observations that heterologous infection of different SARS-CoV-2 variants do not exacerbate disease in subsequent re-infections. The continual emergence of new SARS-CoV-2 variants mandates a better understanding of cross-protection and immune imprinting in infected individuals. Such information is essential to guide vaccine strategy and public policy to emerging SARS-CoV-2 VOCs and future novel pandemic coronaviruses.

ABSTRACT: In the last decade, there has been a significant increase in the demand for small rodents such as hamsters, guinea pigs, rats, and mice to be kept as pets. Consequently, the veterinary care provided to these animals has also increased. The aim of this study was to describe gross, histopathological and immunohistochemical findings of 26 spontaneous neoplasms diagnosed in 25 pet rodents in Northeastern Brazil. A retrospective study was carried out from 2014 to 2022 in two veterinary diagnostic laboratories to identify cases of tumoriform lesions in these species. Hamsters represented the most frequent species in this study (60%, 15/25), followed by rats (28%, 7/25), guinea pigs (8%, 2/25), and mice (4%, 1/25), with a mean age of 17.63 months. The anatomical regions of the face/head and thoracic region were the most affected. The most affected tissues were the skin/subcutaneous/mucosal (65%, 15/26) and mammary gland (23%, 6/26). Eighteen different types of neoplasms were diagnosed, and T-cell lymphomas and mammary adenocarcinomas were the most diagnosed tumors, each corresponding to 12% (3/26) of the cases. Leiomyosarcoma, myxosarcoma and mammary adenocarcinoma metastases were also noted. Immunohistochemistry was essential for the diagnosis of certain malignant mesenchymal and round-cell neoplasms. Pet rodent neoplasms in Northeastern Brazil are common, especially in hamsters, and immunohistochemistry can be a useful tool for the definitive diagnosis of these tumors.

ABSTRACTMultiple vaccines have been developed and licensed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While these vaccines reduce disease severity, they do not prevent infection. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor-binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4 A using cryogenicelectron microscopy. Using this RBD-grafted SpyCage scaffold (RBD + SpyCage), we performed two intranasal vaccination studies in the “gold-standard” pre-clinical Syrian hamster model. The initial study focused on assessing the immunogenicity of RBD + SpyCage combined with the LTA1 intranasal adjuvant. These studies showed RBD + SpyCage vaccination induced an antibody response that promoted viral clearance but did not prevent infection. Inclusion of the LTA1 adjuvant enhanced the magnitude of the antibody response but did not enhance protection. Thus, in an expanded study, in the absence of an intranasal adjuvant, we evaluated if covalent bonding of RBD to the scaffold was required to induce an antibody response. Covalent grafting of RBD was required for the vaccine to be immunogenic, and animals vaccinated with RBD + SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.IMPORTANCEDespite the availability of efficacious COVID vaccines that reduce disease severity, SARS-CoV-2 continues to spread. To limit SARS-CoV-2 transmission, the next generation of vaccines must induce immunity in the mucosa of the upper respiratory tract. Therefore, we performed proof-of-principle, intranasal vaccination studies with a recombinant protein nanoparticle scaffold, SpyCage, decorated with the RBD of the S protein (SpyCage + RBD). We show that SpyCage + RBD was immunogenic and enhanced SARS-CoV-2 clearance from the nose and lungs of Syrian hamsters. Moreover, covalent grafting of the RBD to the scaffold was required to induce an immune response when given via the intranasal route. These proof-of-concept findings indicate that with further enhancements to immunogenicity (e.g., adjuvant incorporation and antigen optimization), the SpyCage scaffold has potential as a versatile, intranasal vaccine platform for respiratory pathogens.

Summary: Background: Pulmonary infection with SARS-CoV-2 stimulates host immune responses and can also result in the progression of dysregulated and critical inflammation. Throughout the pandemic, the management and treatment of COVID-19 has been continuously updated with a range of antiviral drugs and immunomodulators. Monotherapy with oral antivirals has proven to be effective in the treatment of COVID-19. However, treatment should be initiated in the early stages of infection to ensure beneficial therapeutic outcomes, and there is still room for further consideration on therapeutic strategies using antivirals. Methods: We studied the therapeutic effects of monotherapy with the oral antiviral ensitrelvir or the anti-inflammatory corticosteroid methylprednisolone and combination therapy with ensitrelvir and methylprednisolone in a delayed dosing model of hamsters infected with SARS-CoV-2. Findings: Combination therapy with ensitrelvir and methylprednisolone improved respiratory conditions and reduced the development of pneumonia in hamsters even when the treatment was started after 2 days post-infection. The combination therapy led to a differential histological and transcriptomic pattern in comparison to either of the monotherapies, with reduced lung damage and down-regulation of expression of genes involved in the inflammatory response. Furthermore, we found that the combination treatment is effective in case of infection with either the highly pathogenic delta or circulating omicron variants. Interpretation: Our results demonstrate the advantage of combination therapy with antiviral and corticosteroid drugs in COVID-19 treatment from the perspective of lung pathology and host inflammatory responses. Funding: Funding bodies are described in the Acknowledgments section.

Furry animals, such as dogs and cats, are permanently settled in our homes. Many people cannot imagine life without their favorite pet. Unfortunately, the appearance of animals in the human environment is associated with exposure to numerous allergens. Allergy to fur animals is currently a relatively common form of sensitization and affects both adults and children. The possibility of diagnosing sensitization to specific proteins that are found in animal secretions and knowledge about the biological role of these allergens allows patients to give more detailed and adequate recommendations. However, the correct interpretation of sensitization to allergen components is still a challenge for the clinician. In the first part of the review the allergens (accepted by the WHO/IUIS Allergen Nomenclature Committee) of dog, cat, guinea pig, jungle hamster, Syrian hamster, house mouse and rat were characterized. The review article presents a compendium of information about the known allergens, which, we hope, will prove useful in the daily work of an allergist. [ABSTRACT FROM AUTHOR]

Leptospirosis is an important zoonosis that in cattle is characterized as a reproductive disease. It is well reported that the main agent of bovine leptospirosis worldwide is Sejroe serogroup serovar Hardjo. Reproductive disease in cattle has several gaps in its knowledge and studies with Golden Syrian hamsters, experimentally infected, are limited. Therefore, a protocol that could reproduce the chronic genital disease in hamsters would be extremely valuable for the advance of the knowledge of that syndrome. The aim of this study was to establish an experimental protocol for chronic non-lethal genital infection of female hamsters by L. santarosai serovar Guaricura (Sejroe serogroup), strain 2013_VF52. For this, two concentrations (1.0 × 108 leptospires/mL and 1.0 × 104 leptospires/mL) were used intraperitoneally in female hamsters of 06–08 weeks of age. Hamsters that survived for up to forty days after inoculation were euthanized. Uterine and renal tissues were collected to evaluate leptospires' presence by PCR and culture. The protocol demonstrated that 1.0 × 104 leptospires/mL of the strain determined chronic genital leptospirosis in the hamster model. The standardization of a protocol for chronic genital leptospirosis in hamsters can be extremely useful for the understanding of the physiopathology of the infection, as the distribution of leptospires in the uterus and the agent-host interactions. [ABSTRACT FROM AUTHOR]

This study was designed to analyze changes in the spermatozoa of three species of Phodopus hamsters incubated under different conditions. Cauda epididymal sperm were incubated for 4 h in modified Tyrode's medium containing albumin, lactate, pyruvate, and Hepes (mTALP-H), in the same medium with the addition of bicarbonate (mTALP-BH), or with bicarbonate and 20 ng/mL of progesterone (mTALP-BH+P4). Media with bicarbonate are believed to promote capacitation in rodent species. Sperm motility, viability, capacitation patterns, and kinematics were assessed at different times. Capacitation in live cells was quantified after staining with Hoechst 33258 and chlortetracycline. Patterns believed to correspond to non-capacitated cells (F pattern), capacitated, acrosome-intact cells (B pattern), and acrosome-reacted cells (AR pattern) were recognized. Kinematics were examined via computer-assisted sperm analysis (CASA). The results showed a decrease in total motility in all three species in different media, with a sharp decrease in progressive motility in bicarbonate-containing media (without or with progesterone), suggesting hyperactivated motion. However, none of the other signs of hyperactivation described in rodents (i.e., decrease in STR or LIN, together with an increase in ALH) were observed. F pattern cells diminished with time in all media and were generally lower in P. roborovskii and higher in P. campbelli. B pattern cells increased in mTALP-BH media in all species. Progesterone did not enhance the percentage of B pattern cells. Finally, AR pattern cells increased in all species incubated in different media, showing the highest percentage in P. roborovskii and the lowest in P. campbelli. Comparisons between media revealed that there were higher percentages of F pattern cells and lower percentages of B pattern cells over time in medium without bicarbonate (mTALP-H) in comparison to media containing bicarbonate (mTALP-BH; mTALP-BH+P4). Overall, changes consistent with the acquisition of capacitation and development of hyperactivated motility were found; however, further studies are required to better characterize media necessary to support the pathways involved in these processes in Phodopus species. [ABSTRACT FROM AUTHOR]

Background Marburg virus (MARV) has caused numerous sporadic outbreaks of severe hemorrhagic fever in humans. Human case fatality rates of Marburg virus disease (MVD) outbreaks range from 20% to 90%. Viral genotypes of MARV can differ by over 20%, suggesting variable virulence between lineages may accompany this genetic divergence. Comparison of existing animal models of MVD employing different strains of MARV support differences in virulence across MARV genetic lineages; however, there are few systematic comparisons in models that recapitulate human disease available. Methods We compared features of disease pathogenesis in uniformly lethal hamster models of MVD made possible through serial adaptation in rodents. Results No further adaptation from a previously reported guinea pig-adapted (GPA) isolate of MARV-Angola was necessary to achieve uniform lethality in hamsters. Three passages of GPA MARV-Ci67 resulted in uniform lethality, where 4 passages of a GPA Ravn virus was 75% lethal. Hamster-adapted MARV-Ci67 demonstrated delayed time to death, protracted weight loss, lower viral burden, and slower histologic alteration compared to GPA MARV-Angola. Conclusions These data suggest isolate-dependent virulence differences are maintained even after serial adaptation in rodents and may serve to guide choice of variant and model used for development of vaccines or therapeutics for MVD. [ABSTRACT FROM AUTHOR]

The ongoing SARS-CoV-2 epidemic was marked by the repeated emergence and replacement of "variants" with genetic and phenotypic distance from the ancestral strains, the most recent examples being viruses of the Omicron lineage. Here, we describe a hamster direct contact exposure challenge model to assess protection against reinfection conferred by either vaccination or prior infection. We found that two doses of self-amplifying RNA vaccine based on the ancestral Spike ameliorated weight loss following Delta infection and decreased viral loads but had minimal effect on Omicron BA.1 infection. Prior vaccination followed by Delta or BA.1 breakthrough infections led to a high degree of cross-reactivity to all tested variants, suggesting that repeated exposure to antigenically distinct Spikes, via infection and/or vaccination drives a cross-reactive immune response. Prior infection with ancestral or Alpha variant was partially protective against BA.1 infection, whereas all animals previously infected with Delta and exposed to BA.1 became reinfected, although they shed less virus than BA.1-infected naive hamsters. Hamsters reinfected with BA.1 after prior Delta infection emitted infectious virus into the air, indicating that they could be responsible for onwards airborne transmission. We further tested whether prior infection with BA.1 protected from reinfection with Delta or later Omicron sublineages BA.2, BA.4, or BA.5. BA.1 was protective against BA.2 but not against Delta, BA.4, or BA.5 reinfection. These findings suggest that cohorts whose only immune experience of COVID-19 is Omicron BA.1 infection may be vulnerable to future circulation of reemerged Delta-like derivatives, as well as emerging Omicron sublineages. [ABSTRACT FROM AUTHOR]

Introduction: The Severe Acute Respiratory Syndrome-Coronavirus-2 (SARSCoV-2) infection involves pulmonary inflammation that can progress to acute respiratory distress syndrome, a primary cause of lung damage/fibrosis in patients with Coronavirus Disease-2019 (COVID-19). Currently, there is no efficacious therapy available to alleviate lung fibrosis in COVID-19 cases. In this proof-of-concept study, we evaluated the effect of CC-11050, a small molecule phosphodiesterase-4 inhibitor, in dampening lung inflammation and fibrosis in a hamster model of SARS-CoV-2 infection. Methods: Following intranasal inoculation with SARS-CoV-2/WA- 1/2000 strain, hamsters were treated with CC-11050 or placebo by gavage from day-1 until day-16 post-infection (dpi). Animals were monitored for body weight changes, virus titers, histopathology, fibrotic remodeling, cellular composition in the lungs between 2 and 16 dpi. Results: We observed significant reduction in lung viral titer with concomitant reduction in inflammation and fibrotic remodeling in CC-11050 treated hamsters compared to untreated animals. The reductions in immunopathologic manifestations were associated with significant downregulation of inflammatory and fibrotic remodeling gene expression, reduced infiltration of activated monocytes, granulocytes, and reticular fibroblasts in CC-11050 treated animals. Cellular studies indicate a link between TNF-α and fibrotic remodeling during CC11050 therapy. Discussion: These findings suggest that CC-11050 may be a potential hostdirected therapy to dampen inflammation and fibrosis in COVID-19 cases. [ABSTRACT FROM AUTHOR]

Objectives: To study clinical disease outcomes in both human and animal models to understand the pathogenicity of omicron compared to the delta variant. Methods: In this cross-sectional observational study, clinical outcomes of adults who tested positive at 2 testing centres in Delhi National Capital Region between January 2022 and March 2022 (omicron-infected; N = 2998) were compared to a similar geographical cohort (delta-infected; N = 3292). In addition, disease course and outcomes were studied in SARS-CoV-2-infected golden Syrian hamsters and K-18 humanized ACE2 transgenic mice. Results: Omicron variant infection was associated with a milder clinical course [83% (95% CI 61, 94) reduced risk of severity compared against delta] adjusting for vaccination, age, sex, prior infection and occupational risk. This correlated with lower disease index and vir comparing omicron with other variants in animal models. Conclusions: Infections caused by the omicron variant were milder compared to those caused by the delta variant independent of previous immunity. [ABSTRACT FROM AUTHOR]

Abstract This study examined the physiological effects of replacing some of the casein with either a plant based, animal or combination of protein sources in a high-fat diet fed to golden Syrian hamsters. Cooked kidney beans (BN) and beef (Bf) patties drained of fat were fed at 25 and 50% of diet. A combination of BN and Bf (BNBf) was also fed at 25 and 50%. Saturated fat content of the 25% Bf (Bf25) and 50% Bf (Bf50) increased 57 and 215% compared to Control. The Bf diets also increased caloric density compared to the Control. Likewise, the 50% Bn (Bn50) diet had 60% less saturated fat and lower caloric density than the Control. Despite these differences there were no differences in body weight gain or adipose weight between BN of Bf diets and Control. The BN50 diet reduced liver weight and increased caloric intake. The BN diets reduced total plasma cholesterol (TC). The BF diets also reduced TC but the results were not significant. The BN25, BN50 and BNBF50 diets also reduced low density lipoprotein (LDL) cholesterol. The BN and BF50 diets reduced liver fat. The BN diets decreased fecal fat excretion while the BF diets increased excretion. This suggests that increased fat excretion might offset the higher total fat and saturated fat of the BF diets to reduce adverse effects on body weight, adipose weight, and cholesterol. The high-fat content of the base (Control) diet may have muted the effects of the diet treatments. Graphical Abstract

Background: The success of embryo production is largely determined by the accuracy of making medium formulations that are adapted to the age of embryo growth. It is known that the cryopreservation method is widely used for the vitrification of embryos frozen at -196°C. Aims: This study aimed to analyze the embryonic development of mice (Mus musculus L.) and hamsters using culture and vitrification media. Method: This method uses the Preferred Guide to Reporting Items for Systematic Review and Meta-analysis (PRISMA). Results: Based on the search results, a total of 700 articles were obtained which then entered the elimination stage, resulting in 37 articles on the Development of Rat Embryos (Mus musculus L.) and Hamsters Using Culture and Vitrification Media. Conclusion: Thus, it can be concluded that the identification of the embryonic development of mice (Mus musculus L.) and hamsters can be used with the use of culture media and the development of vitrification methods. [Open Vet J 2023; 13(2.000): 143-149]

Social stressors are known to have strong negative impacts on mental health. There is a long history of preclinical social defeat stress studies in rodents focusing on males that has produced important insights into the neural mechanisms that modulate depression- and anxiety-related behavior. Despite these impressive results, a historical weakness of rodent social stress models has been an under-representation of studies in females. This is problematic because rates of depression and anxiety are higher in women versus men. Recently there has been a surge of interest in adapting social stress methods for female rodents. Here we review new rodent models that have investigated numerous facets of social stress in females. The different models have different strengths and weaknesses, with some model systems having stronger ethological validity with other models having better access to molecular tools to manipulate neural circuits. Continued use and refinement of these complementary models will be critical for addressing gaps in understanding the function of neural circuits modulating depression- and anxiety-related behavior in females.

ABSTRACTNipah virus (NiV) is a high-risk pathogen which can cause fatal infections in humans. The Indian isolate from the 2018 outbreak in the Kerala state of India showed ~ 4% nucleotide and amino acid difference in comparison to the Bangladesh strains of NiV and the substitutions observed were mostly not present in the region of any functional significance except for the phosphoprotein gene. The differential expression of viral genes was observed following infection in Vero (ATCC® CCL−81™) and BHK−21 cells. Intraperitoneal infection in the 10–12-week-old, Syrian hamster model induced dose dependant multisystemic disease characterized by prominent vascular lesions in lungs, brain, kidney and extra vascular lesions in brain and lungs. Congestion, haemorrhages, inflammatory cell infiltration, thrombosis and rarely endothelial syncitial cell formation were seen in the blood vessels. Intranasal infection resulted in respiratory tract infection characterised by pneumonia. The model showed disease characteristics resembling the human NiV infection except that of myocarditis similar to that reported by NiV-Malaysia and NiV-Bangladesh isolates in hamster model. The variation observed in the genome of the Indian isolate at the amino acid levels should be explored further for any functional significance.

Simple Summary: Understanding how a virus interacts with cellular targets in an animal model provides critical information in developing therapeutic targets and vaccines for humans. The Syrian hamster model of SARS-CoV-2 infection, the causative agent of COVID-19, is one of the most widely used animal models for this disease. While extensive work on vaccine and therapeutic interventions have been performed in this animal model, the initial viral targets and spread throughout the respiratory tract has been poorly documented. We sought to evaluate the viral spread by microscopic examination of tissues as early as 6 hours post intranasal inoculation through the development of lung lesions at 3 days post inoculation. Coronavirus Infectious Disease 2019 (COVID-19) initiated a global pandemic that thus far has resulted in the death of over 6.5 million people internationally. Understanding the viral tropism during the initial, subclinical phase of infection is critical to develop targeted vaccines and therapeutics. With the continued emergence of variants of concern, particularly those that appear to have a tropism for the upper respiratory tract, understanding the complete pathogenesis is critical to develop more effective interventions. Thus far, the Syrian hamster has served as the most consistent small animal model of SARS-CoV-2 infection for mild to moderate respiratory disease. Herein, we utilize histopathology and immunohistochemistry to characterize the peracute phase of disease initiating at 6-h-post-inoculation in the intranasal inoculation route Syrian hamster model. Inflammation and viral replication initiates in the respiratory epithelium of nasal turbinates as early as 12-h-post-inoculation and moves caudally through the nasal cavity by 36-h-post inoculation. Lower respiratory involvement can be detected as early as 12-h-post inoculation in the intranasal inoculated hamster model. These data highlight the importance of rostral nasal cavity sampling at early timepoints for detection of SARS-CoV-2 in the Syrian hamster model. [ABSTRACT FROM AUTHOR]

Amebiasis is an intestinal infection caused by Entamoeba histolytica. Amebic liver abscess (ALA) is the most common extraintestinal complication of amebiasis. In animal models of ALA, neutrophils have been shown to be the first cells to come into contact with Entamoeba histolytica during the initial phase of ALA. One of the multiple mechanisms by which neutrophils exhibit amebicidal activity is through reactive oxygen species (ROS) and the enzyme NADPH oxidase (NOX2), which generates and transports electrons to subsequently reduce molecular oxygen into superoxide anion. Previous reports have shown that ROS release in the susceptible animal species (hamster) is mainly stimulated by the pathogen, in turn provoking such an exacerbated inflammatory reaction that it is unable to be controlled and results in the death of the animal model. Apocynin is a natural inhibitor of NADPH oxidase. No information is available on the role of NOX in the evolution of ALA in the hamster, a susceptible model. Our study showed that administration of a selective NADPH oxidase 2 (NOX2) enzyme inhibitor significantly decreases the percentage of ALA, the size of inflammatory foci, the number of neutrophils, and NOX activity indicated by the reduction in superoxide anion (O2−) production. Moreover, in vitro, the apocynin damages amoebae. Our results showed that apocynin administration induces a decrease in the activity of NOX that could favor a decrease in ALA progression. [ABSTRACT FROM AUTHOR]

Since SARS-CoV-2 was first reported in late 2019, multiple variations of the original virus have emerged. Each variant harbors accumulations of mutations, particularly within the spike glycoprotein, that are associated with increased viral transmissibility and escape immunity. The different mutations in the spike protein of different variants shape the subsequent antibody and T cell responses, such that exposure to different spike proteins can result in reduced or enhanced responses to heterologous variants further down the line. Globally, people have been exposed and re-exposed to multiple variations of the Ancestral strain, including the five variants of concerns. Studies have shown that the protective immune response of an individual is influenced by which strain or combination of strains they are exposed to. The initial exposure to a specific strain may also shape their subsequent immune patterns and response to later infections with a heterologous virus. Most immunological observations were carried out early during the pandemic when the Ancestral strain was circulating. However, SARS-CoV-2 variants exhibit varying patterns of disease severity, waning immunity, immune evasion and sensitivity to therapeutics. Here we investigated the cross-protection in hamsters previously infected with a variant of concern (VOC) and subsequently re-infected with a heterologous variant. We also determined if cross-protection and immunity were dependent on the specific virus to which the hamster was first exposed. We further profiled the host cytokine response induced by each SARS-CoV-2 variants as well as subsequent to re-infection. A comparative analysis of the three VOCs revealed that Alpha variant was the most pathogenic VOC to emerge. We showed that naturally acquired immunity protected hamsters from subsequent re-infection with heterologous SARS-CoV-2 variant, regardless which variant the animal was first exposed to. Our study supports observations that heterologous infection of different SARS-CoV-2 variants do not exacerbate disease in subsequent re-infections. The continual emergence of new SARS-CoV-2 variants mandates a better understanding of cross-protection and immune imprinting in infected individuals. Such information is essential to guide vaccine strategy and public policy to emerging SARS-CoV-2 VOCs and future novel pandemic coronaviruses. [ABSTRACT FROM AUTHOR]

Prion diseases are progressive neurodegenerative disorders affecting humans and various mammals. The prominent neuropathological change in prion-affected brains is neuroinflammation, histopathologically characterized by reactive gliosis surrounding prion deposition. The cause and effect of these cellular responses are still unclear. Here we investigate the impact of innate immune responses on prion replication using in vitro cell culture models. Hamster-adapted transmissible mink encephalopathy prions, hyper (HY) and drowsy (DY) strains, were assayed for accumulation of pathogenic prion protein (PrPSc) in primary glial cultures derived from 8-day-old hamster pups. The kinetics of PrPSc accumulation largely depended on prion strain and brain regions from where glial cells originated. Glial cells derived from the cerebellum were susceptible to HY, but resistant to DY strain as determined by western blot analysis, immunocytochemistry, and animal bioassay. Glial cells from the cerebral cortex were, however, refractory to both strains. PrPSc accumulation was affected by innate immune modulators. Priming glial cells with lipopolysaccharide decreased prion replication, whereas pre-treatment with dexamethasone, inhibiting innate immunity, increased susceptibility to DY infection. Our results suggest that neuroinflammation resulting from prion infection is a response to resolve and/or prevent prion propagation in the brain. It implies a therapeutic potential of innate immune modulation in the early stages of prion disease. [ABSTRACT FROM AUTHOR]

Entamoeba histolytica (E. histolytica) is a parasite in humans that provokes amoebiasis. The most employed drug is metronidazole (MTZ); however, some studies have reported that this drug induces genotoxic effects. Therefore, it is necessary to explore new compounds without toxicity that can eliminate E. histolytica. Flavonoids are polyphenolic compounds that have demonstrated inhibition of growth and dysregulation of amoebic proteins. Despite the knowledge acquired to date, action mechanisms are not completely understood. The present work evaluates the effect of kaempferol against E. histolytica trophozoites and in the interactions with neutrophils from hamster, which is a susceptibility model. Our study demonstrated a significant reduction in the amoebic viability of trophozoites incubated with kaempferol at 150 μM for 90 min. The gene expression analysis showed a significant downregulation of Pr (peroxiredoxin), Rr (rubrerythrin), and TrxR (thioredoxin reductase). In interactions with amoebae and neutrophils for short times, we observed a reduction in ROS (reactive oxygen species), NO (nitric oxide), and MPO (myeloperoxidase) neutrophil activities. In conclusion, we confirmed that kaempferol is an effective drug against E. histolytica through the decrease in E. histolytica antioxidant enzyme expression and a regulator of several neutrophil mechanisms, such as MPO activity and the regulation of ROS and NO. [ABSTRACT FROM AUTHOR]

Onchocerciasis, the second leading infectious cause of blindness, afflicts approximately 21 million people globally. Its control is limited to the use of the microfilaricidal drugs, ivermectin and moxidectin. Both drugs are unable to kill the adult worms which can survive for up to 15 years in patients, justifying the urgent need for potent and novel macrofilaricides that kill adult worms. The development of such drugs has been hindered by the lack of an appropriate small laboratory animal model to evaluate potential drug candidates in vivo. This study assessed the survival of O. ochengi female worms and their embryos over time in two laboratory rodents: gerbils and hamsters and tested using "proof-of-concept" studies, whether known macrofilaricidal drugs can kill these worms. Animals were surgically implanted with mechanical or collagenase-liberated O. ochengi worm masses, and necropsied at various time points to test for survival. Recovered worm masses were assessed for viability by biochemical analysis (MTT/formazan assay) or fecundity (embryogram). Flubendazole (FBZ) administered at 20 mg/kg body weight was used to validate both rodent models. By day 26 post-implantation of 15 worm masses, a median of 7.00 (4.00–10.00) was recovered from hamsters, and 2.50 (2.00–4.00) from gerbils. Worm masses recovered from gerbils were mostly disintegrated or fragmented, with significantly higher fragmentation observed with collagenase-liberated worm masses. FBZ had no significant effect on the number of worm masses recovered, but enhanced embryo degradation in gerbils and reduced worm mass viability in hamsters. This exploratory study has revealed the gerbil and hamster as permissible rodents to adult female worms of O. ochengi. The hamsters appeared to maintain the worms longer, compared to gerbils. [ABSTRACT FROM AUTHOR]

Background: Available therapeutics for visceral leishmaniasis (VL), a deadly parasitic infection, are usually associated with inadequate efficacy and adverse aftereffects. Further, the primary site of Leishmania parasite are host macrophages resulting in compromised immunity; ensuing marked T-cell immunosuppression. Such settings emphasize the exploration of chemo-immunotherapeutic strategies for improvising the infected person’s immune status with better resolution of infection. Methods: Present work employs the immunization of Leishmania-infected hamsters with Leishmania-derived recombinant aldolase (rLdAld) and enolase (rLdEno) proteins in consort with the sub-optimal dose of Ambisome (2.5 mg/kg). After the completion of immunization, hamsters were sacrificed on day 60 and 90 post infection and different organ samples were collected to perform immunological assay for evaluating the therapeutic efficacy and modulation in protective cellular immune responses. Results: Combining these proteins, particularly rLdAld with Ambisome (2.5 mg/kg), has significantly reduced the parasitic load (∼80%) with remarkable enhancement in DTH and lymphoproliferative responses compared to the infected control and only Ambisome treated groups. Moreover, cytokine levels at RNA and protein levels were noticed to be inclined towards Th-1 phenotype through up-regulation of IFN-γ and TNF-α with significant down-regulation in IL-10 and TGF-β expression, an indication towards the generation of protective immunity against experimental VL. Conclusion: Our experimental findings demonstrated that the chemo-immunotherapeutic approach could be an effective way of controlling human VL infection at minimal dosages of antileishmanial with reduced side-effects and propensity of drug resistance emergence.

Teetat Kongratanapasert,1,&ast; Supasek Kongsomros,2,5,&ast; Nlin Arya,3 Kripitch Sutummaporn,3 Witthawat Wiriyarat,3 Yada Akkhawattanangkul,4 Tussapon Boonyarattanasoonthorn,5 Nithi Asavapanumas,5 Phongthon Kanjanasirirat,6 Ampa Suksatu,2 Khanit Sa-ngiamsuntorn,7 Suparerk Borwornpinyo,6,8 Pornpun Vivithanaporn,5 Somchai Chutipongtanate,5,9 Suradej Hongeng,6,9 Boonsong Ongphiphadhanakul,10 Arunee Thitithanyanont,2 Phisit Khemawoot,5 Piyamitr Sritara10 1Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand; 2Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand; 3Department of Preclinic and Applied Animal Science, Faculty of Veterinary Science, Mahidol University, Nakhonpathom, 73170, Thailand; 4Department of Clinical Medicine and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhonpathom, 73170, Thailand; 5Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samutprakarn, 10540, Thailand; 6Excellence Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; 7Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand; 8Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; 9Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand; 10Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand&ast;These authors contributed equally to this workCorrespondence: Phisit Khemawoot, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakarn, 10540, Thailand, Tel/Fax +66 28395161, Email phisit.khe@mahidol.ac.thBackground: The outbreak of COVID-19 has led to the suffering of people around the world, with an inaccessibility of specific and effective medication. Fingerroot extract, which showed in vitro anti-SARS-CoV-2 activity, could alleviate the deficiency of antivirals and reduce the burden of health systems.Aim of Study: In this study, we conducted an experiment in SARS-CoV-2-infected hamsters to determine the efficacy of fingerroot extract in vivo.Materials and Methods: The infected hamsters were orally administered with vehicle control, fingerroot extract 300 or 1000 mg/kg, or favipiravir 1000 mg/kg at 48 h post-infection for 7 consecutive days. The hamsters (n = 12 each group) were sacrificed at day 2, 4 and 8 post-infection to collect the plasma and lung tissues for analyses of viral output, lung histology and lung concentration of panduratin A.Results: All animals in treatment groups reported no death, while one hamster in the control group died on day 3 post-infection. All treatments significantly reduced lung pathophysiology and inflammatory mediators, PGE2 and IL-6, compared to the control group. High levels of panduratin A were found in both the plasma and lung of infected animals.Conclusion: Fingerroot extract was shown to be a potential of reducing lung inflammation and cytokines in hamsters. Further studies of the full pharmacokinetics and toxicity are required before entering into clinical development.Keywords: Boesenbergia rotunda, Zingiberaceae, panduratin A, SARS-CoV-2, COVID-19, hamster